The present invention relates to novel compounds of [N-benzyl-o-(2,6-dichloroanilino)phenyl]acetic acid derivatives.
It has been known that o-(2,6-dichloroanilino)phenylacetic acid and salts thereof are important medicines having antiinflammatory and analgic effects in Experientia page 450 (1973) by P. J. Krupp, R. M. Gdynia, A. Sallmann, G. Wilhelmi, R. Ziel and R. Jaques.
It has been proposed to produce o-(2,6-dichloroanilino) phenyl acetic acid by the following processes.
(1) Hydrolysis of N-(2,6-dichlorophenyl)indolinone with base British (Pat. No. 1,139,332.
(2) Hydrolysis of o-(2,6-dichloranilino)benzyl cyanide with base British Pat. No. 1,139,332.
(3) Reaction of o-(2,6-dichloroanilino)acetophenone with sulfur and morpholine and hydrolysis of the resulting morpholide British Pat. No. 1,183,968.
In these processes, N-(2,6-dichlorophenyl)anthranilic acid is the starting material.
In the process (1), N-(2,6-dichlorophenyl)indolinone is produced by a reaction by chloroacetyl chloride with 2,6-dichlorodiphenylamine which is produced by a thermal decomposition of N-(2,6-dichlorophenyl)anthranilic acid.
In the process (2), o-(2,6-dichloroanilino)benzyl cyanide is produced by reducing N-(2,6-dichlorophenyl)anthranilic acid with lithium aluminum halide and converting the resulting o-(2,6-dichloroanilino)benzyl alcohol to a halide thereof and then, reacting sodium cyanide.
In the process (3), o-(2,6-dichloroanilino)acetophenone is produced from N-(2,6-dichlorophenyl)anthraniloyl chloride.
In these conventional processes, o-(2,6-dichloroanilino)phenylacetic acid is produced by complex steps from the starting material of N-(2,6-dichlorophenyl)anthranilic acid which is produced by the Ullmann reaction of 2,6-dichloroaniline with 2-halobenzoic acid or the reaction of 2,6-dichloro-1-bromobenzene with anthranilic acid in the presence of a copper type catalyst. However, the yield of the Ullmann reaction is unthinkably low to contaminate impurities and accordingly, the product obtained from N-(2,6-dichlorophenyl)anthranilic acid should be purified by expensive methods to use the product as a medicine.